Genomic instability leads to complex patterns of chromosomal rearrangements in certain cells, e.g., cancer cells. These events are associated with copy number changes as well as translocations and rearrangements affecting multiple chromosomes in a single cell. Array CGH (aCGH) is a widely used technology for investigating genomes of interest. However aCGH data is typically plotted across normal reference chromosomes and does not represent the in vivo structures of chromosomes in cancer cells. Thus structural lesions frequently seen in cancer cells, such as derivative and marker chromosomes, inversions and ring chromosomes cannot be identified in aCGH assays. In addition many of the translocations reported in cancer cells appear to be balanced at the level of resolution provided by the light or fluorescent microscope. Thus the absence of copy number change associated with these lesions obscures them from detection by CGH analyses. In addition to somatically acquired genomic changes recent investigations have identified naturally occurring copy number variants (CNVs) in the human genome that may mediate human variation and disease. These CNVs include duplications, inversions and deletions of variable sizes ranging from cytogenetic bands to individual genes. Although aCGH can measure the copy number variations associated with CNVs, in certain cases it cannot determine the orientation and relative positions of each copy of these variations in a genome.
Cytogenetics is typically used for identifying balanced translocations, marker chromosomes, and other genomic structures present in a sample of interest. Standard cytogenetic assays, such as Giemsa (G) banding have identified numerous cancer-specific translocations and chromosome abnormalities in cancer cells such as the Philadelphia (t9,22) chromosome. Improvements in cytogenetic banding and visualization such as M banding and spectral karyotyping (SKY) have enabled detailed analyses on a chromosome by chromosome basis of inversions and translocations, as well as the identification of regions of losses in cancers of interest. Furthermore these assays provide an assessment of chromosome copy number as well as structural integrity on a cell-by-cell basis in a sample of interest.